Diabetes mellitus (DM) is a disease that causes a pathologic elevation in blood glucose level (glucose concentration in blood) due to impaired insulin secretion or insulin resistance and is known to serve as a risk factor for various serious complications. Diabetes mellitus is reportedly developed by the involvement of various environmental factors (a lack of exercise, overeating, and obesity, etc.) on the basis of genetic factors. The number of diabetes mellitus patients is expected to increase in the future with increases in obese population. Diabetes mellitus is classified into insulin-dependent diabetes mellitus (IDDM) (type 1 diabetes mellitus) and non-insulin-dependent diabetes mellitus (type 2 diabetes mellitus). The great part (about 90%) of diabetes mellitus patients is classified as type 2 diabetes mellitus patients.
Type 1 diabetes mellitus is a disease in which beta cells, which secrete insulin in the pancreatic islets of Langerhans, are killed due to various genetic factors and acquired factors. Type 2 diabetes mellitus is a disease that is caused by insufficient amounts of insulin secreted in response to glucose in beta cells and by reduction in insulin sensitivity in peripheral tissues (liver, muscle, and fat, etc.).
As for the treatment and prophylaxis of diabetes mellitus, diet therapy and exercise therapy as well as medication is practiced.
Examples of current typical medication include medication involving subcutaneously administering insulin, an insulin analog, or a GLP-1 (glucagon-like peptide-1) analog or the like, and medication using an orally administrable hypoglycemic drug. The orally administrable hypoglycemic drug includes sulfonylureas (SU drugs) such as glimepiride and the like; biguanides (BG drugs) such as metformin and the like; alpha-glucosidase inhibitors (alpha-GI drugs) such as voglibose, miglitol, and the like; thiazolidine derivatives (TZD drugs) such as pioglitazone and the like; DPP-IV (dipeptidyl peptidase-IV) inhibitors such as Sitagliptin, Alogliptin, and the like; etc.
Somatostatin is widely distributed in the central nervous system including the hypothalamus and the like, the pancreatic islets of Langerhans, and the intestinal mucosa, etc., and plays an important role in the control of gastrointestinal motility, digestive juice secretion, and glucose or lipid metabolism. Particularly, in living organisms, somatostatin is known to suppressively act on the production or secretion of various hormones, growth factors, and biologically active substances. The hormones on which somatostatin suppressively acts include growth hormone (GH), thyroid stimulating hormone (TSH), prolactin, insulin, glucagon, gastrin, secretin, peptide YY (PYY), gastric inhibitory polypeptide (GIP), GLP-1, GLP-2, cholecystokinin (CCK), vasoactive intestinal peptide (VIP), oxyntomodulin, and the like. In addition, somatostatin also acts as paracrine in the pancreatic islets of Langerhans or the mucosa of gastrointestinal tract where delta cells are in contact with alpha cells and beta cells. Somatostatin therefore has diverse biological functions in the endocrine system, the exocrine system, and the nervous system, etc.
Somatostatin receptor is a seven-transmembrane G protein-coupled receptor. Five subtypes have been found so far and respectively designated as SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 (Non Patent Literature 1). Among them, SSTR5 has been shown to participate in the regulation of insulin and incretin secretions (Non Patent Literature 2).
Meanwhile, Patent Literature 1 has reported that the following compound has an SSTR5 antagonist action:
wherein each Ra is independently selected from the group consisting of a hydrogen atom, a halogen atom, a C1-10 alkyl group, and a halogen atom-substituted C1-10 alkyl group; R1 is selected from the group consisting of a hydrogen atom, substituted phenyl, and a substituted heterocyclic ring; R2 is selected from the group consisting of substituted aryl and a substituted heterocyclic ring; and n and m are each independently selected from the group consisting of 1, 2, and 3.
Patent Literatures 2 and 3 disclose that the following compound has an AMPA receptor inhibitory action and the like and may be used in the treatment of demyelinating disease or neurodegenerative disease:
wherein Q represents NH, O, or S, R1, R2, R3, R4, and R5 each represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or a group represented by the formula —X-A (wherein X represents a single bond, substituted C1-6 alkylene, —O—, —S—, or the like); and A represents a C3-8 cycloalkyl group, a C3-8 cycloalkenyl group, a 5- to 14-membered nonaromatic heterocyclic ring, a C6-14 aromatic ring, or a 5- to 14-membered aromatic heterocyclic ring, provided that three of R1 to R5 are the same or different and each represent —X-A, and each of the remaining two is a hydrogen atom, a halogen atom, or a C1-6 alkyl group.
Patent Literatures 2 and 3 also describe the following compound as one example of the above-mentioned compound in Example 379B:

Li et al. discloses the following compound as to the oxidative conversion of isoxazolidine to isoxazoline (Non Patent Literature 3):

In addition to those mentioned above, the following compounds are known under CAS Registration Nos. 1381469-87-9, 1214501-97-9, and 1214473-59-2:
